There is currently a need in drug discovery and development and in general biological research for methods and apparatus for accurately performing cell-based assays. Cell-based assays are advantageously employed for assessing the biological activity of chemical compounds.
In addition, there is a need to quickly and inexpensively screen large numbers of chemical compounds. This need has arisen in the pharmaceutical industry where it is common to test chemical compounds for activity against a variety of biochemical targets, for example, receptors, enzymes and nucleic acids. These chemical compounds are collected in large libraries, sometimes exceeding one million distinct compounds.
In the field of compound screening, cell-based assays are run on populations of cells. The measured response is usually an average over the cell population. For example, a popular instrument used for ion channel assays is disclosed in U.S. Pat. No. 5,355,215. A typical assay consists of measuring the time-dependence of the fluorescence of an ion-sensitive dye, the fluorescence being a measure of the intra-cellular concentration of the ion of interest which changes as a consequence of the addition of a chemical compound. The dye is loaded into the population of cells disposed on the bottom of the well of a multi-well plate at a time prior to the measurement.
Different assays require different image analysis protocols in order to provide meaningful results. In known image analysis systems, pre-defined image analysis protocols are built-in to the image analysis software systems provided for the purpose of analysing the experimental data produced in an assay. These image analysis protocols are sometimes referred to as “canned” image analysis protocols. The user can typically vary parameters associated with different steps of a canned protocol, in order to fine tune the image analysis and improve the results depending on the conditions and other parameters of their experimental set-up.
International patent publication number WO 00/72258 describes a method for the general purpose analysis of experimental data. A method for the development of image analysis protocols is proposed, in which a user is able to select from a set of predetermined general assay features, including object features, aggregate features and general purpose image processing features. So-called “feature gates” which can be used to define sub-sets of an object population that will contribute to an object or aggregate feature set. Feature gates are defined in terms of a range including a lower and upper limit in the range. However, the flexibility in definition of image processing protocols which can be developed using the proposed system remains relatively limited, particularly when there are objects which are interrelated, such as a cell and its nucleus. Further, the object features for which data can be reported are limited.
It is an object of the invention to provide an improved image analysis protocol development environment which allows users, including users without a computer programming background, to develop their own automated image analysis protocols in a flexible and intuitive manner.